Effect of beta-adrenoceptor activation on [Ca2+]i regulation in murine skeletal myotubes

Am J Physiol. 1999 May;276(5):C1038-45. doi: 10.1152/ajpcell.1999.276.5.C1038.

Abstract

The present study used real-time confocal microscopy to examine the effects of the beta2-adrenoceptor agonist salbutamol on regulation of intracellular Ca2+ concentration ([Ca2+]i) in myotubes derived from neonatal mouse limb muscles. Immunocytochemical staining for ryanodine receptors and skeletal muscle myosin confirmed the presence of sarcomeres. The myotubes displayed both spontaneous and ACh-induced rapid (<2-ms rise time) [Ca2+]i transients. The [Ca2+]i transients were frequency modulated by both low and high concentrations of salbutamol. Exposure to alpha-bungarotoxin and tetrodotoxin inhibited ACh-induced [Ca2+]i transients and the response to low concentrations of salbutamol but not the response to higher concentrations. Preexposure to caffeine inhibited the subsequent [Ca2+]i response to lower concentrations of salbutamol and significantly blunted the response to higher concentrations. Preexposure to salbutamol diminished the [Ca2+]i response to caffeine. Inhibition of dihydropyridine-sensitive Ca2+ channels with nifedipine or PN-200-110 did not prevent [Ca2+]i elevations induced by higher concentrations of salbutamol. The effects of salbutamol were mimicked by the membrane-permeant analog dibutyryl adenosine 3', 5'-cyclic monophosphate. These data indicate that salbutamol effects in skeletal muscle predominantly involve enhanced sarcoplasmic reticulum Ca2+ release.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / pharmacology
  • Adrenergic beta-Agonists / pharmacology
  • Albuterol / pharmacology
  • Animals
  • Animals, Newborn
  • Bucladesine / pharmacology
  • Caffeine / pharmacology
  • Calcium / metabolism*
  • Cells, Cultured
  • Immunohistochemistry
  • Mice
  • Microscopy, Confocal
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / ultrastructure*
  • Myosins / analysis
  • Receptors, Adrenergic, beta / physiology*
  • Ryanodine Receptor Calcium Release Channel / analysis
  • Tetrodotoxin / pharmacology

Substances

  • Adrenergic beta-Agonists
  • Receptors, Adrenergic, beta
  • Ryanodine Receptor Calcium Release Channel
  • Caffeine
  • Tetrodotoxin
  • Bucladesine
  • Myosins
  • Acetylcholine
  • Albuterol
  • Calcium